Using the BCSC signature, we systematically evaluated breast cancer cell responses to chemotherapy in the perspective of BCSCs in vitro and in vivo, elucidated the key role of polyamine anabolism in the regulation of BCSCs, and developed a novel HIF‐1 inhibitor britannin that may specifically eradicate chemotherapy‐induced BCSC enrichment (Figure 4V). The gene discussed is HIF1A; the disease is breast cancer.